Reviewed, UniProtKB/Swiss-Prot Q99988 (GDF15_HUMAN)

Names and origin

Protein names

Recommended name:
    Growth/differentiation factor 15
      Short name=GDF-15
Alternative name(s):
    Placental bone morphogenetic protein
    Placental TGF-beta
    Macrophage inhibitory cytokine 1
      Short name=MIC-1
    Prostate differentiation factor
    NSAID-activated gene 1 protein
      Short name=NAG-1
    NSAID-regulated gene 1 protein
      Short name=NRG-1

Gene names

Name:	GDF15
Synonyms:	MIC1, PDF, PLAB, PTGFB

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	308 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Subunit structure	Homodimer; disulfide-linked By similarity.
Subcellular location	Secreted Probable.
Tissue specificity	Highly expressed in placenta, with lower levels in prostate and colon and some expression in kidney.
Sequence similarities	Belongs to the TGF-beta family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Cytokine Growth factor
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Gene Ontology (GO)
Biological process	cell-cell signaling Ref.3 Traceable author statement. Source: ProtInc transforming growth factor beta receptor signaling pathway Ref.2 Traceable author statement. Source: ProtInc
Cellular component	Golgi apparatus Inferred from direct assay. Source: HPA extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	cytokine activity Ref.3 Traceable author statement. Source: ProtInc growth factor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 29	29	Potential
	Propeptide	30 – 194	165	Potential		PRO_0000033992
	Chain	195 – 308	114	Growth/differentiation factor 15		PRO_0000033993
Amino acid modifications
	Glycosylation	70	1	N-linked (GlcNAc...) Potential
	Disulfide bond	211 ↔ 274		By similarity
	Disulfide bond	240 ↔ 305		By similarity
	Disulfide bond	244 ↔ 307		By similarity
	Disulfide bond	273		Interchain By similarity
Natural variations
	Natural variant	9	1	V → L: dbSNP rs1059519. Ref.2 Ref.3 Ref.4 Ref.6		VAR_047646
	Natural variant	48	1	T → S: dbSNP rs1059369. Ref.4 Ref.1 Ref.5 Ref.7 Ref.8 Ref.9		VAR_010386
	Natural variant	202	1	H → D: dbSNP rs1058587. Ref.1		VAR_047647
Experimental info
	Sequence conflict	269	1	V → E in AAB88913. Ref.1
	Sequence conflict	288	1	T → A in AAF89834. Ref.10

Sequences

	Sequence		Length	Mass (Da)
	Q99988-1 [UniParc]. Last modified November 25, 2008. Version 2. Checksum: 2C28C59020A90238	FASTA	308	34,154
	10 20 30 40 50 60 MPGQELRTVN GSQMLLVLLV LSWLPHGGAL SLAEASRASF PGPSELHTED SRFRELRKRY 70 80 90 100 110 120 EDLLTRLRAN QSWEDSNTDL VPAPAVRILT PEVRLGSGGH LHLRISRAAL PEGLPEASRL 130 140 150 160 170 180 HRALFRLSPT ASRSWDVTRP LRRQLSLARP QAPALHLRLS PPPSQSDQLL AESSSARPQL 190 200 210 220 230 240 ELHLRPQAAR GRRRARARNG DHCPLGPGRC CRLHTVRASL EDLGWADWVL SPREVQVTMC 250 260 270 280 290 300 IGACPSQFRA ANMHAQIKTS LHRLKPDTVP APCCVPASYN PMVLIQKTDT GVSLQTYDDL LAKDCHCI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"PLAB, a novel placental bone morphogenetic protein." Hromas R., Hufford M., Sutton J., Xu D., Li Y., Lu L. Biochim. Biophys. Acta 1354:40-44(1997) [PubMed: 9375789] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS SER-48 AND ASP-202. Tissue: Placenta.
[2]	"Human cDNA encoding a novel TGF-beta superfamily protein highly expressed in placenta." Yokoyama-Kobayashi M., Saeki M., Sekine S., Kato S. J. Biochem. 122:622-626(1997) [PubMed: 9348093] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT LEU-9. Tissue: Fibrosarcoma.
[3]	"MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily." Bootcov M.R., Bauskin A.R., Valenzuela S.M., Moore A.G., Bansal M., He X.Y., Zhang H.P., Donnellan M., Mahler S., Pryor K., Walsh B.J., Nicholson R.C., Fairlie W.D., Por S.B., Robbins J.M., Breit S.N. Proc. Natl. Acad. Sci. U.S.A. 94:11514-11519(1997) [PubMed: 9326641] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT LEU-9.
[4]	"Cloning and characterization of a novel member of the transforming growth factor-beta/bone morphogenetic protein family." Paralkar V.M., Vail A.L., Grasser W.A., Brown T.A., Xu H., Vukicevic S., Ke H.Z., Qi H., Owen T.A., Thompson D.D. J. Biol. Chem. 273:13760-13767(1998) [PubMed: 9593718] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-9 AND SER-48. Tissue: Placenta.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-48. Tissue: Placenta.
[6]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LEU-9.
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT SER-48.
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-48. Tissue: Muscle.
[9]	"Identification of a novel member of the TGF-beta superfamily highly expressed in human placenta." Lawton L.N., de Fatima Bonaldo M., Jelenc P.C., Qiu L., Baumes S.A., Marcelino R.A., de Jesus G.M., Wellington S., Knowles J.A., Warburton D., Brown S., Soares M.B. Gene 203:17-26(1997) [PubMed: 9426002] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 14-308, VARIANT SER-48.
[10]	"Cyclooxygenase inhibitors regulate the expression of a TGF-beta superfamily member that has proapoptotic and antitumorigenic activities." Baek S.J., Kim K.S., Nixon J.B., Wilson L.C., Eling T.E. Mol. Pharmacol. 59:901-908(2001) [PubMed: 11259636] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 264-308.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBLGenBankDDBJ	U88323 mRNA. Translation: AAB88913.1. AB000584 mRNA. Translation: BAA19151.1. AF019770 mRNA. Translation: AAB88673.1. AF003934 mRNA. Translation: AAC24456.1. AK291530 mRNA. Translation: BAF84219.1. BT019465 mRNA. Translation: AAV38272.1. CH471106 Genomic DNA. Translation: EAW84694.1. BC000529 mRNA. Translation: AAH00529.1. BC008962 mRNA. Translation: AAH08962.1. AF008303 Genomic DNA. Translation: AAC39537.1. AF173860 mRNA. Translation: AAF89834.1.
IPI	IPI00306543.
PIR	JC5697.
RefSeq	NP_004855.2.
UniGene	Hs.616962
3D structure databases
HSSP	HSSP built from PDB template 1LXI based on UniProtKB P18075.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q99988. 1 interaction.
Proteomic databases
PeptideAtlas	Q99988.
PRIDE	Q99988.
Genome annotation databases
Ensembl	ENSG00000130513. Homo sapiens. [Contig view]
GeneID	9518.
KEGG	hsa:9518.
Organism-specific databases
GeneCards	GC19P018358.
H-InvDB	HIX0014912.
HGNC	HGNC:30142. GDF15.
HPA	HPA011191.
MIM	605312. gene.
PharmGKB	PA134866647.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q99988.
HOVERGEN	Q99988.
Gene expression databases
ArrayExpress	Q99988.
Bgee	Q99988.
CleanEx	HS_GDF15.
GermOnline	ENSG00000130513. Homo sapiens.
Family and domain databases
InterPro	IPR001839. TGFb. IPR017948. TGFb_CS. [Graphical view]
Pfam	PF00019. TGF_beta. 1 hit. [Graphical view]
ProDom	PD000357. TGFb. 1 hit. [Graphical view] [Entries sharing at least one domain]
PROSITE	PS00250. TGF_BETA_1. False negative. PS51362. TGF_BETA_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	35670.
SOURCE	Search...

Entry information

Entry name

GDF15_HUMAN

Accession

Primary (citable) accession number: Q99988
Secondary accession number(s): O14629 , P78360, Q9BWA0, Q9NRT0

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	November 25, 2008
Last modified:	June 16, 2009
This is version 81 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)